During the past four decades, an obscure disease of sheep called "scrapie" has emerged as an important area of biochemical research. Transmission studies and neuropathological examination of brain tissue suggest that scrapie is a prototype for the spongiform encephalopathies of man, i.e., kuru and Creutzfeldt-Jakob disease. Prior to the transmission of the kuru and Creutzfeldt-Jakob diseases to chimpanzees by intracerebral inoculation of infected brain, both of these diseases were classified as "degenerative" abiotrophies of the nervous system. To date, the chemical nature of the scrapie agent remains obscure. The unusual physico-chemical properties of the scrapie agent and its slow replication in the absence of any detection by host defense mechanisms suggest that scrapie is a novel infectious entity. Unlike viruses, the scrapie agent cannot be visualized by electron microscopy and its presence does not provide a detectable immunological response. Our research program is directed toward understanding the chemical structure of the scrapie agent. Because the present assay for scrapie requires determination of an end-point by titration in mice over 9 months, we plan to devote considerable effort to the search for a more rapid and less expensive biological assay. Concurrently, we plan to develop a reliable method for the partial purification of the scrapie agent and to use this preparation to explore chemical and immunological assay systems. The purification and subsequent elucidation of the chemical structure of the scrapie agent promises to bring new concepts and techniques to several areas of molecular biology and medicine.